Pathogenesis: A History of the World in Eight Plagues

by Jonathan Kennedy

According to Sigmund Freud, there have been three great revolutions in Western science and each of these dealt a blow to humans’ belief in their special status—or what he referred to as our “naive self-love.”[1]

The realization that we aren’t even in control of our thought processes was, he argued, the “most irritating insult” to “the human mania of greatness.”

If we trace the Tree of Life to the base of its trunk, we find the Last Universal Common Ancestor (LUCA): a single-celled, bacterium-like organism that is the distant progenitor of all living things, humans included. This one shared antecedent is the reason why everything from blue whales to giant redwoods to bacteria have inherited common features such as DNA to store genetic information and a molecule called ATP that is the universal source of energy.

The American paleontologist Stephen Jay Gould argues that “on any possible, reasonable, or fair criterion, bacteria are—and always have been—the dominant forms of life on earth.”[8] One reason for this is the sheer length of time they have existed.

Such immense periods of time are hard for the human brain to conceptualize, but if we compressed 4.6 billion years into one calendar year then bacteria evolved in early spring. Humans don’t appear until about half an hour before midnight on 31 December.[11]

About 2.5 billion years ago our world was almost completely submerged in water, with the exception of the odd volcanic peak piercing through the sea.[14] Methane in the atmosphere created a greenhouse effect that kept the planet far hotter than it is today. There was little or no free oxygen in the water or air, as it was all locked up in other molecules. Life on earth consisted of anaerobic bacteria.

In total, phytoplankton—photosynthesizing microorganisms in the sea—account for at least half of the oxygen produced by living organisms.[17]

Instead, viruses consist of genetic material—in the form of DNA or its sister molecule RNA—coated in protein. On their own they are an inert arrangement of matter. But when they manage to enter—or infect—the cell of a living thing, they take over its machinery to reproduce copies of themselves, bursting into life.

Viruses are so minuscule that they haven’t left a mark on the fossil record. Their origins remain unclear.

But only about 220 types of virus are known to be capable of infecting humans.[20]

A retrovirus is a specific type of virus that reproduces by inserting a copy of its DNA into the genome of the host cell. But when a retrovirus infects a sperm or egg cell, something remarkable happens: viral DNA is then passed on to every cell in every subsequent generation. An astonishing 8 percent of the human genome is made up of such genes.[22]

One remarkable example is a gene inherited from a retrovirus infection about 400 million years ago that plays a crucial role in memory formation. The gene does this by coding for tiny protein bubbles that help to move information between neurons, in a manner similar to the way that viruses spread their genetic information from one cell to another.[23] In the laboratory, mice that had this gene removed are unable to form memories.

There is nothing like this interface between the placenta and womb anywhere else in our bodies. When geneticists looked at the gene responsible for creating it, they realized that it was almost identical to those used by retroviruses to produce the proteins that attach to cells they are infecting without triggering an immune response.[24] The scientists concluded that a crucial function of the placenta didn’t emerge gradually as a result of evolution by natural selection but was suddenly acquired when a retrovirus inserted its DNA into our ancestor’s genome. If one of our distant ancestors hadn’t been infected by a virus hundreds of millions of years ago, humans would reproduce by laying eggs.

In the parts of human cells that interact with viruses, it has been estimated that viruses account for 30 percent of all genetic mutations since our species’ divergence from chimpanzees.[25]

This suggests that humans’ struggle for existence was a fight against microbes rather than alpha males and apex predators.

Each of us hosts an estimated 40 trillion bacteria—meaning they slightly outnumber human cells.[28] Viruses? At least ten times that figure. In total, the human microbiome—all the microbes living in our body—weighs around the same as our brain, between one and two kilos.[29]

The study that inspired the editors to write this piece analyzed bacteria in the feces of more than 2,000 Belgians.[31] Of over 500 strains of bacteria they tested, more than 90 percent were able to produce neurotransmitters like dopamine and serotonin that play a key role in regulating human moods.

The main alternative to the Great Men theory of history is what Lucien Febvre, the French historian, referred to in the early 1930s as “histoire vue d’en bas et non d’en haut,” or “history from below and not from above.”[35] This approach focuses on the masses of ordinary men and women, often fighting against exploitation and oppression. In this view, it is the cumulative impact of all their struggles that drives progressive social, political and economic transformations.

Over the last two decades, scientists have discovered several more species of humans that were alive at the same time as Homo sapiens. Denisovans split from Neanderthals not long after they’d ventured out of Africa and went on to occupy the eastern part of Eurasia. The only physical traces of this species are a few bone fragments uncovered in caves in the Altai Mountains and on the Tibetan plateau. Anatomically, Denisovans would have looked similar to Neanderthals although they appear to have had much bigger teeth, and they carried a number of gene mutations, including one that affected red blood cells and allowed them to live comfortably at high altitudes.[5]

Homo floresiensis lived on the Indonesian island of Flores. They are colloquially referred to as Hobbits on account of their height—they stood just over a meter tall—and disproportionately long feet.[6] One theory suggests that Homo floresiensis is descended from Homo erectus, who arrived there about a million years ago and then became isolated by deep waters.[*1]

Homo luzonensis is another extinct, small-bodied human species that was discovered in 2019 on the island of Luzon, in the Philippines. Their curved fingers and toe bones suggest that they retained...

Then, between 50,000 and 40,000 years ago, something astonishing happened. Within a few thousand years, Homo sapiens burst out of Africa and quickly spread across the world—from western Europe all the way to Australia. At the same time, all other species of human vanished from the face of the earth.[8]

Why this happened is one of the biggest mysteries of human prehistory.

The Venus of Hohle Fels, a statuette with ballooning breasts and an elaborately carved vulva, is the first undisputed depiction of a human being.[15]

In addition, several flutes carved from mammoth ivory and animal bone that date to around 40,000 years ago have been discovered in German caves, including Hohle Fels. This is the earliest evidence of humans playing music.[17]

Our species is said to have triumphed over all others because it was uniquely capable of what paleoanthropologists—researchers concerned with the origins and development of early humans—call “symbolic behavior.”

The ability to think and behave in complex ways allowed us to plan, cooperate and out-compete the bigger, stronger Neanderthals, as well as other humans who did not possess these skills.[21]

The idea of the cognitive revolution is conveniently Eurocentric. It locates modern-day France and Germany as the site of the metamorphosis of human behavior and identifies the first Homo sapiens capable of symbolic thought as those who left Africa and then turned left when they reached the Levant.

However, there isn’t clear evidence that the anatomy of our brains changed around this time.[24]

Conservative paleontologists working in cahoots with the Catholic Church made a concerted effort to emphasize the differences between the two species. By portraying Neanderthals as only very distantly related to Homo sapiens, they hoped to retain our status as a separate and exceptional species.

When the first complete skeleton of a Neanderthal was discovered by three Catholic priests in 1908 in La Chapelle-aux-Saints in southern France—about 300 kilometers west of Chauvet—the Church made sure it ended up in the hands of someone who shared their worldview, Marcellin Boule, director of the Laboratory of Paleontology at Muséum d’Histoire Naturelle in Paris, reconstructed the specimen so that it looked much more simian than human, with its forward-jutting head, slouching shoulders, hunched spine, bent knees and even opposable toes. Boule’s work was flawed, but it had a profound impact on scientific understanding of Neanderthals for the next half-century and it still informs the popular stereotype of the ape-like cave man.[27]

Although no one uses this term anymore, the public’s understanding has not really moved on and the received wisdom still holds that we are superior.

Over the past couple of decades, however, it has become increasingly clear that Neanderthals were capable of all sorts of sophisticated behaviors that until recently were only associated with Homo sapiens. There is archeological evidence that Neanderthals manufactured stone tools requiring cognitive skill and dexterity,[31] made fire on demand,[32] sailed from mainland Europe to Crete and the Ionian Islands,[33] produced glue from the bark of the birch tree,[34] and appear to have treated maladies with medicinal plants that had anesthetic and antibiotic properties: traces of DNA from poplar trees, which contain salicylic acid—the naturally occurring inspiration for the synthetic aspirin, and Penicillium mold, the source of penicillin—have been found in the calcified plaque of Neanderthals.[35]

In 2018, researchers used uranium-thorium dating to estimate the age of the thin crusts of minerals that have formed on top of the paintings.[45] The paintings turned out to be at least 65,000 years old—making them the earliest known examples of cave art anywhere in the world. This was 10,000 years before the first indication that Homo sapiens lived in western Europe, meaning that these Paleolithic doodles must have been made by Neanderthals.[46]

Bearing in mind the overwhelming lack of evidence, you might be wondering why anyone still thinks that there is a significant cognitive gap between Neanderthals and Homo sapiens. The answer seems to be blind prejudice.

While this might not sound like much, we don’t all have the same bits of Neanderthal DNA and when we pool all these gene variants they account for about 40 percent of the Neanderthal genome[53]—providing incontrovertible evidence that the two species not only met, but had sex and reproduced. Neanderthal males coupled up with Homo sapiens females and vice versa.[54] Interbreeding happened over tens of thousands of years, but the most active period of mating was between about 50,000 and 60,000 years ago.[55]

When scientists looked at the calcified plaque of a 48,000-year-old Neanderthal’s teeth, they found the DNA of a strain of archaea called Methanobrevibacter oralis that is present in the mouths of humans today and is associated with gum disease.[56] After comparing the Neanderthal sample with a modern strain, it became clear that the microbes’ last common ancestor lived about 120,000 years ago. As that is several hundred thousand years after Neanderthals and Homo sapiens diverged, the germ must have been transmitted between the two species. The most likely way this happened was through kissing or perhaps sharing food. This suggests that the liaisons between Neanderthals and Homo sapiens were consensual—in

This demonstrates that Homo sapiens’ early incursions out of Africa into the Eastern Mediterranean did not develop into a permanent move. Instead, Homo sapiens advanced and then retreated, and Neanderthals expanded into areas that they once occupied. It is more evidence—if the reader needs it—that Homo sapiens were not innately superior to Neanderthals.

After they reproduced, Homo sapiens retained certain Neanderthal gene variants which helped them to survive as they migrated northward. Geneticists call this “adaptive introgression”—and it is the closest that humans can get to the process of horizontal gene transfer, which allows different species of bacteria to exchange DNA in order to adjust to new environmental challenges.

As a result, infectious diseases created an “invisible barrier”: it was impossible for Homo sapiens to migrate out of Africa because sooner or later they would encounter Neanderthals and their pathogens and get ill, and the same was true when Neanderthals pushed southward.[60] For early humans, the Eastern Mediterranean region must have seemed like a cursed realm, the Paleolithic equivalent of Tolkien’s Mordor.[*3]

But if adaptive introgression helped both species to build up immunity to each other’s diseases, why did Homo sapiens prevail and Neanderthals disappear? To answer this question we need to consider how climate impacts the prevalence of infectious disease.

The Last Glacial Period—which lasted from around 110,000 to 12,000 years ago—covered much of North Eurasia in ice and made it difficult for Neanderthals to survive.

DNA analysis of a female Neanderthal who was alive over 50,000 years ago in the Altai Mountains demonstrates that her parents were half-siblings and that mating between close relatives had been common among her recent ancestors.[72]

The impact of the glacial period would have been far less catastrophic in Africa, where Homo sapiens still lived. Food would have remained abundant and the fall in temperature made the climate more favorable.

The vast majority of pathogens that are capable of infecting humans are zoonotic—that is, they originate in animals and then jump the species barrier to infect us.

Homo sapiens, whose ancestors had lived in Africa for millions of years, carried a far greater disease load than Neanderthals, who had inhabited Europe for hundreds of thousands of years.

When Homo sapiens gained immunity to Neanderthal diseases between 50,000 and 40,000 years ago, they were finally able to migrate northward out of Africa into areas inhabited by Neanderthals without getting horribly ill. The curse that had made the Eastern Mediterranean all but uninhabitable for tens of thousands of years was lifted. Our ancestors traveled deep into Eurasia, where they encountered Neanderthal and Denisovan communities that had never been exposed to African pathogens and hadn’t had the opportunity to build up any tolerance. Within a relatively short period of time all other human species died out and were replaced by the newly ubiquitous Homo sapiens.

Stonehenge wasn’t built by the earliest people to permanently inhabit the British Isles. It was constructed by farmers who originated in Anatolia and arrived in northwestern Europe about 6,000 years ago and almost completely replaced the genetically distinct hunter-gatherer population who had lived there since the end of the Ice Age.

Within a century or two of the great sarsen stones being put in place the monument builders’ ancestors were replaced by another new, genetically and culturally distinct group that forms the basis of the current population of the United Kingdom. So even those white British people who claim to be the indigenous population are not directly related to the builders of Stonehenge.

Prehistory was punctuated by massive waves of migration that resulted in a new population moving into a region and almost completely wiping out the previous inhabitants. Nearly always, the migrants were unwittingly aided by an invisible but devastating weapon of mass destruction: infectious diseases to which they were to some extent immune but to which original communities had little or no resistance. In addition to novel pathogens, Neolithic immigrants brought new genes, new languages and new ideas such as farming and metallurgy.